Cancer Pain

Over one-third of patients with cancer, and around three-quarters of those with advanced disease, have chronic pain. Currently available opioid therapies do not yield sufficient relief in a substantial proportion of these patients and there is a clear need for new treatments.

Chronic, unremitting pain in deep tissues that results from cancer adversely affects a disproportionately large portion of the population. Worldwide, more than 12.7 million people are diagnosed with cancer each year (WHO cancer factsheet 2008) and it has been estimated that by 2020 that figure will rise to more than 16 million people a year. The prevalence of cancer pain directly correlates with the stage of disease, with more than 70% of patients in the advanced stages of cancer reporting pain (World Health Organization, 1996). In particular, patients with breast and prostate cancer, both of which have a propensity to spread to bone, more often experience pain than patients with uterine and cervical cancer. Pain as an initial presenting symptom will occur in 20-40% of patients. Severe pain occurs in 20-35% of the cancer population and significantly impairs activities of daily living. The mean incidence of pain in a sample of 5,410 patients (across 22 studies) in various stages of cancer was 51%, whereas among 9,007 patients (across 38 studies) with advanced metastatic or a terminal phase of cancer, the mean incidence was 74% (Bonica, 1990).

Currently, opioids are the principal agents employed in the management of cancer pain, but the therapeutic benefit of their prolonged use is frequently offset by the development of undesirable effects such as constipation, sedation, respiratory depression and tolerance (Kehl et al., 2003).

Sativex® for Cancer Pain

Sativex® is approved in Canada as an adjunctive analgesic treatment in adult patients with advanced cancer who experience moderate to severe pain during the highest tolerated dose of strong opioid therapy for persistent background pain.

Cancer pain is also the lead target indication for approval of Sativex in the US.

GW is evaluating Sativex in a Phase 3 program to treat persistent pain in people with advanced cancer who experience inadequate pain relief from optimized chronic opioid therapy. This program represents the lead target indication for Sativex in the United States and is also intended to form the basis for future regulatory applications in the rest of the world. This Phase 3 program follows positive data from two Phase 2 trials of Sativex in this indication involving over 530 patients.

GW believes that Sativex has the potential to address a significant unmet need in this large market by treating patients with a product that employs a differentiated non-opioid mechanism of action, and offers the prospect of pain relief without increasing opioid-related adverse side effects. The primary treatment for cancer pain is analgesic narcotics, also known as opioids. Morphine and oxycodone are the most prescribed opioids, and morphine is the standard regimen for treating cancer pain in palliative care and hospice care programs and facilities. Opioids are often added to non-opioid analgesics and other adjuvant medications to control cancer pain. The use of opioids is frequently met with undesirable side effects such as constipation, sedation, respiratory depression and analgesic tolerance as well as the risk of addiction. There are currently no approved non-opioid treatments for patients who do not respond to, or experience negative side effects with, opioid medications. Additionally, studies in animal models of pain suggest that there may be pharmacodynamic synergy between cannabinoids and opioids.

Patients are being recruited into these two Phase 3 trials at hospital sites in the United States, Europe and Mexico. Professor Marie Fallon, Professor of Palliative Care, University of Edinburgh, is the principal investigator of the first trial, and Dr. Russell K. Portenoy, Chairman of the Department of Pain Medicine and Palliative Care, Beth Israel Medical Center in New York City, is the principal investigator of the second trial.

GW anticipates that top-line results from at least one of these Phase 3 trials will be available towards the end of 2014, with top-line results from the second Phase 3 trial following shortly thereafter. This program is intended to support the submission of an NDA with the FDA and in other markets around the world.